Criteria For Transplantation Research Articles

P-936. Incidence and Risk Factors for Ventricular Assist Device Infections: A Retrospective Review from the Middle East Gulf Region

Abstract Background A ventricular assist device (VAD) is either a destination therapy or a bridge to heart transplant for patients with end-stage heart failure. Unfortunately, VAD infections are a major complication postimplant. We aimed to evaluate the incidence, risk factors, and outcomes for patients with VAD infections. Baseline characteristics and risk factors for patients implanted with ventricular assist device. Methods We performed the single-center, observational, retrospective study on all patients who underwent VAD implantation between May 2016 and August 2022 with a minimum of 12-month follow-up post-placement. We defined VAD infections according to the International Society of Heart and Lung Transplantation (ISHLT) criteria, classifying infections into VAD-specific and VAD-related. We included all patients above 18 years of age with VAD and excluded patients who underwent VAD implantation outside our facility. Results We included 29 VAD patients, of which 16 were HeartMate 3 left ventricular assist devices (LVADs), 12 were HeartWare ventricular assist devices (HVADs), and one was a biventricular assist device (BiVAD). We reported an overall incidence of 41.3% (n=12/29) of VAD infections during the study period. Within one year post-implantation, we had two VAD-specific driveline infections, which isolated Pseudomonas aeruginosa and methicillin-sensitiveStaphylococcus aureus from the pus culture, and seven VAD-related infections (mediastinitis and bloodstream infections). Bloodstream infections included coagulase-negative staphylococci (n=4), Klebsiella pneumonia (n=1), andCandida tropicalis (n=1). We also had three patients with driveline infections one year after implantation. There were 15 patients requiring extracorporeal membrane oxygenation (ECMO) and one on Impella®. The mean (SD) length of stay during VAD infection was 56.5 (±37.6) days, all-cause mortality for patients with VAD infections was 41.6% (n=5/12), and the overall all-cause mortality in our study was 44.8% (n=13/29). Conclusion The VAD infections for patients on additional cardiac implantable electronic devices, multiple device reinterventions, or requiring temporary mechanical support complicate the overall outcome. Further studies with a larger population from the region are necessary to make better decisions about preventing and treating VAD infections. Disclosures All Authors: No reported disclosures

Identifying the greatest surgeon-perceived barriers and challenges in performing corneal transplantation in India.

There is currently no systematic method of assessing limitations in performing corneal transplantation. The purpose of the study was to identify the limitations of performing corneal transplantation in India. Cross-sectional survey study. A total of 148 members of the Cornea Society of India. A survey tool was developed to identify region-specific barriers to performing corneal transplantation. The survey was edited by a marketing firm and reviewed and approved by 4 of the participating corneal surgeons in India. The electronic survey was distributed nationwide to members of the Cornea Society of India between January 1, 2021 and July 1, 2021. Participants were asked to rate the difficulty or ease of 11 predetermined steps/variables of the corneal transplantation process using a Likert scale. One hundred forty-eight practicing cornea surgeons participated in the survey (21% response rate). The most common barrier was difficulty with finding donors who fulfilled the screening criteria for transplantation (55%). The second most common barrier was patient/family willingness to donate organs (32%). The third most common barrier was the inability to store tissue after it was prepared by the eye bank (20%). The two variables least commonly identified as barriers were operating room staff availability and using the donor tissue before expiration. The greatest barrier to corneal transplantation in India was finding donors who fulfilled screening criteria. Additional studies into the contributing factors are underway to inform governing bodies on resource allocation to enhance procurement of quality donor tissues.

Comprehensive Non-invasive Versus Invasive Approach to Evaluate Cardiac Allograft Vasculopathy in Heart Transplantation: The CCTA-HTx Study.

Coronary computed tomography angiography (CCTA) is emerging as a valuable tool for noninvasive surveillance of cardiac allograft vasculopathy (CAV) in patients with heart transplant (HTx). We assessed the diagnostic performance of a comprehensive CCTA-based approach compared with the invasive reference, which includes invasive coronary angiography, intravascular ultrasound, and fractional flow reserve, for detecting CAV. This was a multicenter prospective study including 37 patients with HTx who underwent CCTA, invasive coronary angiography, intravascular ultrasound, and fractional flow reserve. The comprehensive CCTA-based approach included quantitative and qualitative plaque analysis and functional assessment by fractional flow reserve derived from coronary computed tomography. CAV was diagnosed based on invasive coronary angiography (International Society for Heart and Lung Transplantation criteria) and intravascular ultrasound. Univariable logistic regression analysis was performed to test CCTA-derived predictors of CAV. The area under the curve and accuracy indicators were calculated to evaluate the performance and best cutoffs of CCTA predictors of CAV. The median interval between CCTA and HTx was 5 years. Among the 37 recipients, 23 (62.2%) were diagnosed with CAV. The integration of diameter stenosis and plaque morphology (including plaque burden at minimum lumen area >42% and percent atheroma volume >23%) at CCTA yielded the highest diagnostic performance (accuracy, 84%; sensitivity, 83%; specificity, 86%). The integration of ∆fractional flow reserve derived from coronary computed tomography trans-vessel gradient led to increased sensitivity, albeit with decreased specificity and overall accuracy. The noninvasive approach was associated with a lower contrast and radiation dose, compared with the invasive approach. A noninvasive strategy based on CCTA is accurate for managing patients with HTx. CCTA might be considered the preferred imaging modality for annual CAV surveillance after the first year post-HTx.

Brief Report: Unmet Need for Solid Organ Transplantation Among People With HIV and End-Stage Kidney or Liver Disease: A Brief Report From the HIV Outpatient Study, 2009–2023

Background: Persons with HIV (PWH) with end-stage kidney disease (ESKD) who are eligible for kidney transplantation have post-transplantation outcomes similar to those without HIV infection. However, barriers to referral for care, evaluation, and receipt of transplants remain for PWH. We sought to identify PWH with ESKD or end-stage liver disease (ESLD) who would be candidates for organ transplant and to review their clinical outcomes. Methods: We analyzed data from participants in the HIV Outpatient Study (HOPS) between January 1, 2009, and June 30, 2023, with a diagnosis of ESKD or ESLD. We identified a subset of PWH who would otherwise meet the general criteria for kidney or liver transplantation. Targeted clinical outcomes included dialysis, transplantation, and death. Results: Among 5215 PWH in the HOPS, 258 with ESKD and 23 with ESLD would otherwise meet the criteria for transplant. However, only 9 kidney and 2 liver transplants were performed. Conclusions: Low transplantation rates among eligible PWH suggest that timely referral for care and evaluation for kidney and liver transplantation often does not occur. Expanding access for PWH with ESKD to both deceased and living donor kidney allografts is needed. Kidney and liver transplant centers also need to seek ways to broaden access for eligible PWH with ESKD or ESLD.

Impact of donor obesity on outcomes of donation after circulatory death heart transplantation.

In the setting of the obesity epidemic and donor organ shortage in the United States, there is a growing need to expand the donor organ eligibility criteria for orthotopic heart transplantation (OHT). Donation after circulatory death (DCD) has emerged as a promising solution, but the outcomes with obese donor hearts in DCD OHT remains unknown. Using the United Network for Organ Sharing registry between 2019 and 2024, recipients of DCD OHT were stratified into 3 donor obesity categories by body mass index (BMI): underweight/normal (BMI <25kg/m2), overweight (BMI 25-30kg/m2), and obese (BMI >30kg/m2). These cohorts were subgrouped by organ procurement strategy: direct procurement and preservation (DPP) or normothermic regional perfusion (NRP). Recipient and donor characteristics and risk factors for mortality were analyzed using Cox regression hazard models. Survival at 30days, 1year, and 5years post-transplantation were analyzed using the Kaplan-Meier method. We found no significant differences in patient and graft survival between donor BMI categories at all time points. Among recipients of overweight (hazard ratio [HR], 0.38; P=.0371) and obese (HR, 0.24; P=.0493) donor hearts, NRP was associated with decreased risk of mortality. Donor-recipient predicted heart mass (PHM) undermatching (defined as <86%) was associated with increased risk of mortality among underweight/normal weight donors (HR, 1.28; P=.0323) and overweight donors (HR, 1.08; P=.0382). Donor obesity does not confer an increased risk of recipient mortality in DCD OHT, particularly when NRP is used. PHM undermatching continues to be associated with adverse outcomes in DCD OHT.

Bioactive ECM-mimicking nerve guidance conduit for enhancing peripheral nerve repair

Extensive research efforts are being directed towards identifying alternatives to autografts for the treatment of peripheral nerve injuries (PNIs) with engineered nerve conduits (NGCs) identified as having potential for PNI patients. These NGCs, however, may not fulfill the necessary criteria for a successful transplant, such as sufficient mechanical structural support and functionalization. To address the aforementioned limitations of NGCs, the present investigation explored the development of double cross-linked hydrogels (o-CSMA-E) that integrate the biocompatibility of porcine tendon extracellular matrix (ECM) with the antimicrobial and conductive properties of methacrylated quaternary chitosan. The hydrogels had matrices that could promote the growth of axons and the transmission of neural signals. The hydrogels were subsequently incorporated into a nanofibrous PLLA-ZnO sheath scaffold (ZnO@PLLA) to emulate the natural nerve structure, guiding cell growth and facilitating nerve regeneration. The collaboration of core and sheath materials in ZnO@PLLA/o-CSMA-E nerve guidance conduits resulted in enhanced migration of Schwann cells, formation of myelin sheaths, and improved locomotion performance in rats with sciatic nerve defects when in vivo studies were undertaken. Notably, the in vivo studies demonstrated the similarity between the newly developed engineered NGCs and autologous transplants, with the newly engineered NGCs possessing the potential to promote functional recovery by mimicking the tubular structure and ECM of nerves.

Paediatric acute liver failure: early outcome and evaluation of transplantation criteria in a Belgian transplantation centre

BackgroundOne of the challenges when caring for children admitted for acute liver failure (ALF) is to quickly identify those who will improve spontaneously and those for whom liver transplantation (LT) is the only therapeutic option.MethodsRetrospective study to review our experience, identify mortality risk factors and update our LT criteria in case of paediatric ALF.Results111 children were admitted between March 1989 and May 2021 (mean age 59.1 months). 28 children never met our LT criteria; 17 had contraindication to LT; 66 were registered on the LT waitlist. 14 of these 66 were subsequently withdrawn because of spontaneous liver function recovery; 11 died before having received a liver; 41 were transplanted. Hospital survival rate was 63% for the whole series, 98% for the children without LT criteria and 71% for the transplanted children. Univariate analysis identified cardiovascular and respiratory failures on admission, and grade 4–5 hepatic encephalopathy (HE) during stay significantly associated with death. Non-survivors also had, on admission and during their stay, significantly higher levels of lactate, ammonia and bilirubin and, during their stay, significantly more frequent prothrombin time ≤ 25% or international normalized ratio ≥ 4.0 than the survivors. Multivariate analysis identified grade 4–5 HE, lactate level on admission and ammonia peak level as significant mortality risk factors.ConclusionOur criteria identified almost all children who had the capacity to spontaneously recover their liver function and suggest that updated criteria should combine biological tests and signs of multiple organ failure.

Bronchoscopic Lung Volume Reduction: Effect on Symptoms and Lung Function in Patients With Emphysema That Qualify for Lung Transplant

BackgroundBronchoscopic lung volume reduction (BLVR) studies excluded patients meeting the listing criteria for lung transplantation (LT). Research QuestionWhat are the outcomes of BLVR in a sicker group of emphysematous patients compared to patients not meeting the criteria for LT listing? Study Design and MethodsReal-world retrospective study (June 2018 to December 2022) assessing the effect of BLVR in patients with severe emphysema considered for LT. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLco), symptoms, and 6-minute walk distance (6-MWD) were measured at baseline and 45 days and 6 months post-BLVR. ResultsOf 76 fully evaluated patients (median age 62 years old, 60% female), 42 underwent BLVR (30 sicker patients met the criteria for LT listing). At baseline, patients that met the criteria for listing had shorter baseline 6-MWD (234.72 ± 68.86, p < 0.001), higher BODE index (6.79 ± 1.11, p = 0.001), and lower FEV1 (617.5 ± 139.2 mL, p = 0.005). All patients treated with BLVR experienced a decrease in BODE index and Borg dyspnea by -0.5 to -2 points, respectively. DLco %pred increased by 4.5%, FEV1 increased by 115 mL, FVC increased by 450 mL, and 6-MWD increased by 20 meters. In the sicker group, FEV1 at 45 days post-BLVR increased by 180.8 ± 231 mL (FEV1 %pred 5.84 ± 5.66) compared to baseline; a persistent effect was seen at 6 months in 62% of patients with available data (18/30). Median hospital length of stay was 3.27 ± 3.07 days. Valves were removed in 6 patients (3 in each group) due to complications. The pneumothorax rate was 24% (10/42; 5 in each group). InterpretationsImprovement in lung function after BLVR was observed regardless of disease severity. BLVR might represent an alternative to LT for some patients.

The patient's mental health from the perspective of consultation-liaison psychiatry at the stage of qualification for mechanical circulatory support implantation.

During qualification for mechanical circulatory support, the comprehensive assessment of a patient's mental state is an integral element of the overall medical evaluation. It encompasses a range of psychosocial issues, and as such provides information helpful in the selection of a suitable candidate for the required treatment, and sometimes identifies contraindications to it. It allows ensuring that the patient meets expectations regarding both mental health stability and adherence to medical recommendations. It is also helpful in an early detection and diagnosis of mental problems before the surgery, which can increase the possibility of implementation of appropriate treatment and intervention. Due to the lack of generally accepted guidelines, this assessment can be subjective to some extent, especially if it takes place outside experienced transplant centres. This article presents the core principles of mental status evaluation and psychosocial factors increasing the risk of poor prognosis in this group. The article aims to share with psychiatrists and psychologists the clinical experience and comprehensive knowledge about psychosocial eligibility criteria for mechanical circulatory support or heart transplantation.

Impact of Allogeneic Stem Cell Transplant on Safety and Outcomes of Chimeric Antigen Receptor T Cell (CAR-T) Therapy in Patients with Multiple Myeloma (MM).

Background: Allogeneic stem cell transplantation (allo-SCT) has seen limited use in treating multiple myeloma (MM), despite its potential to offer long-term survival or even cure through the graft-versus-myeloma effect. Its limited application is largely due to concerns over serious complications like infections and graft-versus-host disease (GVHD). The possibility of GVHD exacerbation when CAR-T cells are administered to patients previously treated with allo-SCT remains a topic of concern. Ciltacabtagene autoleucel (Cilta-cel) and idecabtagene vicleucel (Ide-cel) are CAR-T therapies that have been FDA-approved for relapsed/refractory (R/R) MM. A recent study using data from the CARTITUDE-1 trial has shown promising safety and efficacy of Cilta-Cel in patients with a prior history of allo-SCT. This report outlines our real-world experience with CAR-T treatment in such patients. The objective of this study is to assess the safety and effectiveness of CAR-T therapy in R/R MM patients who have previously undergone allo-SCT. Methods: We conducted a retrospective analysis of adult patients (18-70 years old) with R/R MM treated with CAR-T therapy as part of an institutional IRB-approved protocol. Data were collected on safety and efficacy outcomes from the institution's records. Adverse events (AEs) were evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Efficacy metrics included overall response rate (ORR) and progression-free survival (PFS), analyzed through the Kaplan-Meier method, with PFS defined as the time from CAR-T initiation to disease progression or death. Results: Of the 56 patients treated with CAR-T therapy, 8 (14.3%) had previously undergone allo-SCT. These patients had a median of seven prior therapy lines (LOTs), compared to five LOTs in the non-allo-SCT group (p = 0.04). CAR-T infusion occurred a median of 98.8 months after allo-SCT, with a range from 57.9 months to 178.5 months. CRS occurred in 87.5% of the allo-SCT group versus 77.1% in the non-allo-SCT group (p = 0.48). One patient in the allo-SCT group developed hemophagocytic lymphohistiocytosis (HLH), requiring anakinra. At a median follow-up of 4.8 months, the ORR was 87.5% in the allo-SCT group versus 75% in the non-allo-SCT group (p = 0.4). Median PFS had not been reached for the allo-SCT group at the time of analysis compared to 11.9 months in the non-allo-SCT group (p = 0.5). No treatment-related mortality or acute GVHD was noted in the allo-SCT cohort. Conclusions: The study suggests that prior allo-SCT does not adversely affect the safety or efficacy of CAR-T therapy in patients with R/R MM. These findings highlight the need for further investigations with larger patient samples and longer follow-up to better understand the interaction between allo-SCT and CAR-T therapy.

Pathologist interrater reliability and clinical implications of elevated donor-derived cell-free DNA beyond heart transplant rejection, on behalf of the GRAfT investigators

BackgroundThere is significant variability amongst pathologists in the histopathological interpretation of the endomyocardial biopsy (EMB) for acute cellular rejection (ACR) and assessment of variability in the interpretation of antibody-mediated rejection (AMR) has not been reported. In contemporary practice, the strategy of allograft surveillance with donor-derived cell-free DNA (dd-cfDNA) as compared to EMB has not been compared with a focus on long-term clinical outcomes beyond acute rejection (AR). MethodsThe Genomic Research Alliance for Transplantation (GRAfT) is a multicenter, prospective cohort study that enrolled patients from 2015 to 2020. The center pathologist read was compared to two blinded core cardiac pathologists. ACR and AMR were graded based on the International Society for Heart and Lung Transplantation (ISHLT) criteria. Weighted Cohen’s kappa (κ) was used to evaluate interrater reliability between the center and core reads. To assess long-term outcomes, we evaluated a composite of AR, allograft dysfunction, and mortality within 1 year. ResultsThe study included 94 patients (median age 55 years [IQR 45, 62]), 30% female, 41% Black race) with a total of 429 EMBs and paired dd-cfDNA measures. The concordance rate between center and core pathologists was 77% for ACR (95%CI: 66% - 89%) and 63% for AMR (95%CI: 53% - 74%). 46 patients had an elevation in dd-cfDNA without AR by EMB. The median dd-cfDNA was 0.49% (IQR: 0.35, 1.01) and subsequent AR, allograft dysfunction, or mortality occurred in 59% of these patients at 1 year. In patients with AR by EMB and negative dd-cfDNA (n=5) the composite outcome occurred in 20% of patients at 1 year. At baseline, the positive likelihood ratio (LR+) of dd-cfDNA to detect AR by the center pathologist was 3.74 (95% CI 3.01 - 4.64) and core pathologist was 2.59 (95%CI: 1.95 - 3.45). If the composite outcome was included as a true positive, the LR+ of dd-cfDNA improved to 9.82 (95%CI: 7.04, 13.69) and7.63 (95% CI: 5.61, 10.38) at 1-year, respectively. ConclusionsPathologists interrater reliability is limited in both ACR and AMR. The positive LR of dd-cfDNA when compared to traditional histopathology is limited, but when longitudinal clinical outcomes are included to assess diagnostic performance, the LR+ improves significantly. The value of dd-cfDNA extends beyond the diagnosis of AR to include other clinically meaningful outcomes for patients after heart transplant.

Multidisciplinary approaches to downstaging hepatocellular carcinoma: present and future.

Downstaging of hepatocellular carcinoma (HCC) is typically defined as the reduction in size or number of viable tumors through locoregional therapy (LRT), aiming to meet the established criteria for liver transplantation (LT). According to the Barcelona Clinic Liver Cancer (BCLC) staging system, a subgroup of patients with BCLC-B may benefit most from downstaging therapies. The United Network Organ Sharing downstaging protocol identifies potential candidates for downstaging by setting out 'inclusion criteria' and defining 'successful downstaging.' Additionally, the protocol considers factors related to tumor biology, such as an alphafetoprotein level <500 ng/mL after LRT. Reports indicate that successful downstaging rates following LRT are about 50%, with post- LT recurrence rates comparable to those of patients within the Milan criteria. A comprehensive multicenter US study on 10-year outcomes post-LT after downstaging showed 10-year post-LT survival and recurrence rates of 52.1% and 20.6%, respectively, for patients whose disease was downstaged; this compares to 61.5% and 13.3% for those consistently within the Milan criteria. Recently, the development of effective systemic treatments for HCC, such as immuno-oncologic agents, has provided additional opportunities for downstaging. Numerous clinical trials are exploring a multidisciplinary approach (MDA) combining LRT and systemic therapy. Although concrete evidence of the superiority of MDA for HCC downstaging is lacking, some retrospective studies and phase I and II trials have shown promising results regarding the efficacy and safety of MDA for this purpose. In this review, we will also discuss the future of MDA protocols in downstaging for improved clinical outcomes.

Benign pericholecystic regeneration mimicking hepatocellular carcinoma: a potential pitfall in imaging of cirrhosis.

Several pseudolesions mimicking malignancy have been reported in cirrhotic and non-cirrhotic livers. Pericholecystic regeneration is among those pseudolesions and can occasionally mimic malignancy. Herein we present a case series comprised of 10 cirrhotic patients (majority due to alcoholic liver disease [ALD] or metabolic dysfunction associated steatotic liver disease [MASLD]) with pericholecystic observations initially categorized as highly suspicious for HCC (LR-4 and LR-5) due to their suspicious enhancement pattern which were later proven to be benign based on biopsy, transplantation or imaging criteria (stability of size and morphology on serial CT or MRI for > 2 years). These observations ranged 2-6.3cm in size, were multiple in most patients and universally resulted in indentations of gallbladder. Arterial phase hyperenhancement and washout, features usually attributed to hepatocellular carcinoma (HCC), were seen in most patients. However, ancillary features of malignancy such as diffusion restriction, increased T2 signal, and hypointensity on hepatobiliary phase MRI were not present. Pericholecystic observations, in particular in the setting of ALD and MASLD, should be carefully assessed and possibility of pseudolesion should be considered especially when the observations are multiple, cause indentation of gallbladder, and lack ancillary features of malignancy.

The rising cost of liver transplantation in the United States.

Liver transplantation (LT) is the only curative treatment for end-stage liver disease and significantly improves patient outcomes. However, LT is resource-intensive and costly, with expenditures rising dramatically in recent years. Factors contributing to this increase in cost include expanded transplant criteria, utilization of marginal organs, and broader organ distribution, resulting in significant logistical expenses. Advanced technologies like organ perfusion devices, while promising better outcomes, further inflate costs due to their high price and market monopolization. Moreover, living donor liver transplant (LDLT) and utilization of donation after cardiac death (DCD) organs introduce higher initial expenditures yet potential long-term savings. Despite rising costs, reimbursement has remained largely stagnant, putting financial strain on transplant programs, and threatening their sustainability. This review examines the multifaceted drivers of rising costs in LT, focusing on recent policy changes, the role of organ procurement organizations (OPOs) and the impact of new technologies. We also propose comprehensive solutions at national, OPO, and local levels, including optimizing resource allocation, leveraging regional collaborations, and advocating for revised reimbursement models to curb escalating costs. Addressing these challenges is critical to ensuring the continued viability of LT programs and maintaining patient access to this life-saving intervention.

Transcriptomic signatures during normothermic liver machine perfusion correspond with graft quality and predict the early graft function

A better understanding of the molecular events during liver normothermic machine perfusion (NMP) is warranted to develop a data-based approach for the identification of biomarkers representative of graft quality and posttransplant outcome. We analysed the dynamic transcriptional changes during NMP and linked them to clinical and biochemical parameters. 50 livers subjected to NMP for up to 24h were enrolled. Bulk RNA sequencing was performed in serial biopsies collected pre and during NMP, and after reperfusion. Perfusate was sampled to monitor liver function. qPCR and immunohistochemistry were performed to validate findings. Molecular profiles were compared between transplanted and non-transplanted livers, and livers with and without early allograft dysfunction. Pathways related to immune and cell stress responses, cell trafficking and cell regulation were activated during NMP, while cellular metabolism was downregulated over time. Anti-inflammatory responses and genes involved in tissue remodelling were induced at later time-points, suggesting a counter-response to the immediate damage. NMP strongly induced a gene signature associated with ischemia-reperfusion injury. A 7-gene signature corresponds with the benchmarking criteria for transplantation or discard at 6h NMP (area under curve 0.99). CD274 gene expression (encoding programmed cell-death ligand-1) showed the highest predictive value. LEAP2 gene expression at 6h NMP correlated with impaired graft function. Assessment of gene expression markers could serve as a reliable tool to evaluate liver quality during NMP and predicts early graft function after transplantation. The research was supported by "In Memoriam Dr. Gabriel Salzner Stiftung", Tiroler Wissenschaftsfond, Jubiläumsfonds-Österreichische Nationalbank and MUI Start grant.

Coronary and Systemic Vasodilator Responsiveness of Patients Receiving Conventional Intermittent or Nocturnal Hemodialysis.

Nocturnal hemodialysis (nHD) restores the attenuated brachial artery vasodilator responsiveness of patients receiving conventional intermittent hemodialysis (iHD). Its impact on coronary vasodilatation is unknown. We evaluated 25 patients on hemodialysis who fulfilled transplant criteria: 15 on iHD (4-hour sessions, 3 d/wk) and 10 on nHD (≈40 h/wk over 8-10-hour sessions) plus 6 control participants. Following diagnostic angiography, left anterior descending (LAD) coronary flow reserve and mean luminal diameter were quantified at baseline and during sequential intracoronary administration of adenosine (infusion and bolus), nitroglycerin (bolus), acetylcholine (infusion), acetylcholine coinfused with vitamin C, and, finally, sublingual nitroglycerin. Coronary flow reserve in those receiving nHD was augmented relative to iHD (3.28±0.26 versus 2.17±0.12 [mean±SEM]; P<0.03) but attenuated, relative to controls (4.80±0.63; P=0.011). Luminal dilatations induced by intracoronary adenosine and nitroglycerin were similar in nHD and controls but blunted in the iHD cohort (P<0.05 versus both). ACh elicited vasodilatation in controls but constriction in both dialysis groups (both P<0.05, versus control); vitamin C coinfusion had no effect. Sublingual nitroglycerin increased mid-left anterior descending diameter and reduced mean arterial pressure in controls (+15.2±2.68%; -16.00±1.60%) and in nHD recipients (+14.78±5.46%; -15.82±1.32%); iHD responses were markedly attenuated (+1.9±0.86%; -5.89±1.41%; P<0.05, all comparisons). Coronary and systemic vasodilator responsiveness to both adenosine and nitroglycerin is augmented in patients receiving nHD relative to those receiving iHD, whereas vasoconstrictor responsiveness to acetylcholine does not differ. By improving coronary conduit and microvascular function, nHD may reduce the cardiovascular risk of patients on dialysis.

Conversion Therapy to Transplant or Surgical Resection in Patients with Unresectable Hepatocellular Carcinoma Treated with Boosted Dose of Yttrium-90 Radiation Segmentectomy.

The aim of this study was to assess the efficacy of boosted dose yttrium-90 radioembolization (TARE) as a modality for conversion therapy to transplant or surgical resection in patients with unresectable hepatocellular carcinoma (HCC). In this single-center retrospective study, all patients with a diagnosis of HCC who were treated with boosted dose TARE (>190 Gy) between January 2013 and December 2023 were reviewed. Treatment response and decrease in tumor size were assessed with the RECIST v1.1 and mRECIST criteria. Milan and University of California, San Francisco (UCSF), criteria were used to determine transplant eligibility, and Barcelona Clinic Liver Cancer (BCLC) surgical resection recommendations were used to evaluate tumor resectability. Thirty-eight patients with primary HCC who were treated with boosted dose TARE were retrospectively analyzed. The majority of the patients were Child-Pugh A (n = 35; 92.1%), BCLC C (n = 17; 44.7%), and ECOG performance status 0 (n = 25; 65.8%). The mean sum of the target lesions was 6.0 cm (standard deviation; SD = 4.0). The objective response rate (ORR) was 31.6% by RECIST and 84.2% by mRECIST. The disease control rate (DCR) was 94.7% by both RECIST and mRECIST. Among patients outside of Milan or UCSF, 13/25 (52.0%, Milan) and 9/19 (47.4%, UCSF) patients were successfully converted to within transplant criteria. Of patients who were initially unresectable, conversion was successful in 7/26 (26.9%) patients. This study provides further real-world data demonstrating that boosted-dose TARE is an effective modality for conversion of patients with unresectable HCC to transplant or resection.

Evolving trends in liver transplantation eligibility: A shift toward inclusivity for older adults at a Canadian Transplant Center

Background: The surge of end-stage liver disease among older individuals challenges traditional age-based criteria for liver transplantation (LT), historically capped at 65 years. Our Canadian center shifted away from using chronologic age as an absolute refusal criterion since 2019, enabling those aged 65 years and older to seek LT. This study aimed to investigate temporal trends in the transplant care cascade for patients aged 65 and older at our center, pre- and post-clinical shift. Methods: A retrospective study in a single Canadian transplant center reviewed LT referrals between 2015 and 2023, analyzing proportions of patients aged 65 and above at each stage. Specific intervals, 2015–2018 and 2019–2023, were defined for pre- and post-comparisons. Results: Among the 1,007 LT referrals, 11% (n = 110) were patients aged ≥65 years, with 74% ( n = 81) of them being referred after 2019. From 2015 to 2023, older patient proportions increased at all stages of the transplant care cascade: referrals (7.4% to 12.6%), evaluations (7.6% to 11.4%), waitlisting (5.6% to 15.4%), and transplantations (5.8% to 17.5%). Post-clinical shift, the proportion of older patients referred nearly doubled (7.5% vs 13.7%; p &lt; 0.05), with a similar increase in transplants (5.7% vs. 11.5%; p &lt; 0.05). Conclusions: Removing the age cap increased older patient engagement in the LT care cascade. This emphasizes the crucial role of actively promoting awareness of evolving LT eligibility criteria. Concerted efforts should focus on improving transplantation accessibility in older patients, ensuring age alone does not impede the process.

Quality and stability studies of red blood cell concentrates from umbilical cord blood compared to their adult counterparts.

Prematurity is a significant health issue due to its incidence and associated complications. Anemia is common in extremely preterm infants (EPI) and often requires transfusions. Red blood cells (RBC) from adult blood (AB) donors have been linked to oxygen-related complications in EPI, leading to the exploration of cord blood (CB) as an alternative source. However, standardization of CB-RBC manufacturing and comparison with AB-RBC characteristics are necessary before clinical studies can be conducted. This study investigated the quality and characteristics of leukoreduced, gamma-irradiated CB-RBC obtained using a commercial closed system from CB donations not meeting hematopoietic transplantation criteria. CB-RBC units were compared with AB-RBC units, both stored in saline-adenine-glucose-mannitol (SAGM). Various parameters, including hematological and biochemical characteristics, pH, 2,3-DPG levels, blood gases and potential toxicants, were evaluated during storage. CB-RBC units had acceptable initial quality parameters and a hematocrit (55±2%) comparable to AB-RBC. The main finding during storage was a faster rise in hemolysis compared to AB-RBC. Potassium (K+) significantly increased during storage in both sources. As expected, glucose levels decreased, and conversely, lactate levels increased, indicating similar patterns of anaerobic glycolysis during storage. pH decreased, affecting the oxygen dissociation curve due to reduced 2,3-DPG levels. After irradiation at 14 days of storage, CB-RBC were less stable as hemolysis and K+ significantly increased compared to AB-RBC at 24 hours. Phthalate concentrations, indicative of plasticizers, increased during storage, but significantly less in CB compared to AB-RBC. Most metals measured were within acceptable ranges. The quality of CB-RBC during storage is primarily influenced by levels of hemolysis and extracellular K+ content. Based on the analyzed parameters, we suggest that the expiration date for CB-RBC stored with SAGM should be set at 14 days, with transfusion occurring within <24 hours after irradiation.

Benefits of liver transplant in critically ill patients with acute-on-chronic liver failure: Implementation of an urgent living-donor program

We evaluated the liver transplantation (LT) criteria in acute-on-chronic liver failure (ACLF), incorporating an urgent living-donor LT (LDLT) program. Critically ill patients with a Chronic Liver Failure Consortium (CLIF-C) ACLF score (CLIF-C_ACLF_score) ≥65, previously considered unsuitable for LT, were included to explore the excess mortality threshold of the CLIF-C_ACLF_score (CLIF-C_ACLF_score_threshold). We followed 854 consecutive patients with ACLF (276 ACLF grade 2 and 215 ACLF grade 3) over 10 years among 4432 LT recipients between 2008 and 2019. For advanced ACLF patients without immediate deceased-donor (DD) allocation, an urgent LDLT program was expedited. The CLIF-C_ACLF_score_threshold was determined by the metrics of transplant survival benefit: >60% 1-year and >50% 5-year survival rate. In predicting post-LT mortality, the CLIF-C_ACLF_score outperformed the (model for end-stage liver disease-sodium) MELD-Na and (model for end-stage liver disease) MELD-3.0 scores but was comparable to the Sundaram ACLF-LT-mortality score. A CLIF-C_ACLF_score ≥65 (n = 54) demonstrated posttransplant survival benefits, with 1-year and 5-year survival rates of 66.7% and 50.4% (P < .001), respectively. Novel CLIF-C_ACLF_score_threshold for 1-year and 5-year mortalities was 70 and 69, respectively. A CLIF-C_ACLF_score-based nomogram for predicting survival probabilities, integrating cardiovascular disease, diabetes, and donor type (LDLT vs DDLT), was generated. This study suggests reconsidering the criteria for unsuitable LT with a CLIF-C_ACLF_score ≥65. Implementing a timely salvage LT strategy, and incorporating urgent LDLT, can enhance survival rates.